This invention provides a method of treating inflammatory conditions, ameliorating ischemia-induced cell damage and treating muscular dystrophy in mammals.
Mammals, both humans and animals, are known to suffer from various conditions involving inflammation with concomitant swelling, tenderness, decreased mobility, pain, and fever. While a number of anti-inflammatory agents are effective in the symptomatic treatment of such inflammatory conditions as rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, degenerative joint diseases, and the like, many such agents have a number of undesirable side effects, such as gastric irritation and the like.
The etiology and pathogenesis of rheumatic and arthritic diseases remain obscure. Meanwhile, the need continues for safer, better calibrated drugs which will slow the process and alleviate the symptoms of inflammatory diseases. For example, in rheumatoid arthritis, any agent which reduces the inflammation is important in lessening or delaying the development of crippling.
A variety of therapeutic approaches have also been tried in order to prevent ischemia-induced cell damage. Such approaches have not provided a totally satisfactory method for ameliorating ischemia-induced cell damage to date.
Finally, a variety of therapeutic approaches have also been employed to treat muscular dystrophy in mammals. Again, to date none of these approaches has proven totally satisfactory.
It is an object of this invention to provide a new method for treating inflammatory conditions, and slowing the development of arthritic conditions, which method comprises administering a compound selected from among certain phenols and benzamides of the general formula ##STR1## It is a further object of this invention to provide a new method of preventing ischemia-induced cell damage in mammals, which method comprises administering a compound selected from among certain phenols of the general formula set forth above.
Yet another object of this invention is to provide a new method for treating muscular dystrophy in mammals, which method comprises administering a compound selected from among certain phenols of the general formula set forth above to a mammal having muscular dystrophy.
The objects of the present invention employ certain phenols and benzamides of the general formula ##STR2## Such compounds are known in the art and have been found to possess various utilities.
U.S. Pat. No. 3,305,483 discloses that certain phenols of the above formula can be used as an antioxidant for various substances such as gasoline, diesel fuel, heating oil, lubricating oil, asphalt, petroleum wax and high molecular weight hydrocarbon polymers. Chemical Abstracts, 97, 200429m (1982) teaches that 4-(2-dimethylaminoethyl)-2,6-di-t-butylphenol can be used as an antioxidant for jet aircraft fuel. European Patent Application 42,589 describes the use of various of the above phenols as antioxidants for polymeric norbornene type materials.
Chemical Abstracts, 88, 38847m (1978) discloses that 2,6-di-t-butyl-4-[N,N-bis(2-hydroxyethyl)aminomethyl]phenol can be used to increase the heat resistance of certain fibers. Chemical Abstracts, 88, 192135j (1978) teaches that 1-phenyl-4-(3,5-di-t-butyl-4-hydroxybenzyl)piperazine is a noncolorizing thermostabilizer for stress-stable polystyrene. 2-(3,5-Di-t-butyl-4hydroxyphenyl)ethylmethylamine is described as being useful for improving the lightfastness of dyed polyester fibers in Chemical Abstracts, 76, 73628q (1972).
Chemical Abstracts, 77, 141203v (1972) teaches that 3-(dimethylamino)propylaminobis(4-methylene-2,6-di-t-butylphenol can be used to improve the aging resistance of diene rubber. Chemical Abstracts, 91 212411p (1979) describes a 1:1 pyrocatechol/4-[(dimethylamino)methyl]-2,6-di-t-butylphenol complex which deactivates transition metals in rubber. N,N-dimethyl-3,5-di-t-butyl-4-hydroxybenzylamine is disclosed to be an effective polymerization inhibitor for styrene in Chemical Abstracts, 100, 35563w (1984). Chemical Abstracts, 107, 42468s (1987) discloses that 3-(4-hydroxy-3,5-di-t-butylphenyl)-1-aminopropane acetate or N-(4-hydroxy-3,5-di-t-butylbenzyl)-N-(.beta.-aminoethyl)piperazine hydrochloride can be used to modify cation exchange resins so as to reduce the diffusive permeability of the resin membrane and increase its sodium ion transport properties.
Several of the phenols and benzamides of the general formula set forth above have also been found to possess various pharmacological activities. U.S. Pat. No. 3,809,761 discloses that certain of the above phenols can be used to reduce mammalian plasma lipid levels. Chemical Abstracts, 73, 86385w (1970) and Chemical Abstracts, 66, 16925d (1967) teach that certain of the above phenols have antitumor activity. Chemical Abstracts, 74, 96312e (1971) discloses that (4-hydroxy-3,5-di-t-butylbenzyl)methylamine hydrochloride increases the antioxidative activity of liver lipids, thereby increasing liver tissue regeneration following a partial hepatectomy. N-methyl-3,5-di-t-butyl-4-hydroxybenzylamine is said to be able to increase the rate of blood deoxygenation in Chemical Abstracts, 78, 132326f (1973). Finally, Chemical Abstracts, 109, 129047u (1988) discloses that certain benzamides of the above formula are useful for treating epilepsy and high blood pressure.
The phenols and benzamides employed in the methods of the present invention have not heretofore been used to treat inflammatory conditions, prevent ischemia-induced cell damage or treat muscular dystrophy in mammals. The known activities of such compounds, as set forth above, in no way suggest the methods of the present invention. Accordingly, an object of the present invention is to provide new pharmacological uses for certain known phenols and benzamides.
Other objects, features and advantages of the present invention will become apparent from the subsequent description and the appended claims.